Alzamend Neuro™ has licensed from the University of South Florida an ionic cocrystal of lithium for the treatment of Alzheimer’s disease (“AD”). Lithium salts have a long history of human consumption beginning in the 1800’s. In psychiatry, they have been used to treat mania and as a prophylactic for depression since the mid-20th century. Today, lithium salts are used as a mood stabilizer for the treatment of bipolar disorder and dementia. With this in mind, a research team at the University of South Florida have designed, synthesized and characterized a new ionic cocrystal of lithium, LiProSal™ which has exhibited improved pharmacokinetics compared to current FDA-approved lithium drugs as well as bioactive in many in vitro models of AD. LiProSal™ is targeted to be a major improvement over current lithium-based treatments and may also constitute a means of treating Alzheimer’s disease.
Despite these effective medicinal uses, current FDA-approved lithium pharmaceutics (lithium carbonate and lithium citrate) are limited by a narrow therapeutic window that requires regular blood monitoring of plasma lithium levels and blood chemistry by a clinician to mitigate adverse events. Because conventional lithium salts (carbonate and citrate) are eliminated relatively quickly, multiple administrations throughout the day are required to safely reach therapeutic plasma concentrations. However, existing lithium drugs such as lithium chloride and lithium carbonate suffer from chronic toxicity, poor physicochemical properties and poor brain bioavailability. Because lithium is so effective at reducing manic episodes in patients with bipolar disorder, it is still used clinically despite its narrow therapeutic index. This has led researchers to begin to look for alternatives to lithium with similar bioactivities.
The research team at USF developed a new lithium cocrystal composition and method of preparation that requires lower dosages to achieve therapeutic brain levels of lithium for use as a treatment, broadening lithium’s therapeutic index. The compound offers improved physiochemical properties compared to existing forms of lithium, giving it the potential to be developed as an anti-suicidal drug or for use against mood disorders. Recent evidence suggests that lithium may be efficacious for both the treatment and prevention of Alzheimer’s disease. Unlike traditional medications which only address a single therapeutic target, lithium appears to be neuroprotective through several modes of action. For example, it exerts neuroprotective effects, in part, by increasing a brain-derived neurotrophic factor leading to restoration of learning and memory. Another neuroprotective mechanism of lithium is attenuation of the production of inflammatory cytokines like IL-6 and nitric oxide in activated microglia. Moreover, recent clinical studies suggest that lithium treatment may reduce dementia development while preserving cognitive function and reducing biomarkers associated with AD.